Antibiofilm Activity of Heather and Manuka Honeys and Antivirulence Potential of Some of Their Constituents on the DsbA1 Enzyme of Pseudomonas aeruginosa.

Oscar Shirlaw,Lisa Hughes,Veronique Seidel,Rana M Qasaymeh,Georgios Efthimiou,Baraa Attar,Zara Billah

doi:10.3390/antibiotics9120911

Abstract

Heather honey was tested for its effect on the formation of biofilms by Staphylococcus aureus, Pseudomonas aeruginosa, Escherichia coli, Klebsiella pneumoniae, Enterococcus faecalis, Salmonella Enteriditis and Acinetobacter baumanii in comparison with Manuka honey. At 0.25 mg/mL, Heather honey inhibited biofilm formation in S. aureus, A. baumanii, E. coli, S. Enteriditis and P. aeruginosa, but promoted the growth of E. faecalis and K. pneumoniae biofilms. Manuka honey inhibited biofilm formation in K. pneumoniae, E. faecalis, and S. Enteriditis, A. baumanii, E. coli and P. aeruginosa, but promoted S. aureus biofilm formation. Molecular docking with Autodock Vina was performed to calculate the predictive binding affinities and ligand efficiencies of Manuka and Heather honey constituents for PaDsbA1, the main enzyme controlling the correct folding of virulence proteins in Pseudomonas aeruginosa. A number of constituents, including benzoic acid and methylglyoxal, present in Heather and/or Manuka honey, revealed high ligand efficiencies for the target enzyme. This helps support, to some extent, the decrease in P. aeruginosa biofilm formation observed for such honeys.

Highlights

Antimicrobial drug resistance, in Gram-negative bacteria, is an ever-increasing challenge for healthcare systems worldwide [1]
Optimal biofilm formation (OD550 nm 0.8–1.7) by all bacterial species was obtained after a 24 h incubation period
We have shown that benzoic acid and other small molecules including MGO have the potential to target virulence in P. aeruginosa

Summary

Introduction

Antimicrobial drug resistance, in Gram-negative bacteria, is an ever-increasing challenge for healthcare systems worldwide [1]. Alternative treatment options to conventional antibiotics are urgently needed to tackle this global threat [2,3] This includes the discovery of molecules that could disrupt the ability of pathogens to produce virulence factors [4,5]. In Gram-negative bacteria, various virulence factors are produced under the control of a master virulence regulatory oxidoreductase enzyme called DsbA. The latter catalyses the formation of disulfide bonds in proteins and, in doing so, is instrumental to the process of correct protein folding of bacterial virulence proteins, including type-IV fimbriae, flagellae and adhesion factors that play a central role in biofilm formation [6,7,8,9,10,11]. The disulfide bond forming pathways in Gram-positive bacteria are less well established [12]

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Conclusion